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Aluminium in brain tissue in autism
... We sincerely hope that scientists and doctors especially pediatricians, after taking notice of our work [19,27] and including this one, will implement our proposal for the removal of aluminum from vaccines and its replacement with Calcium Phosphate as the adjuvant which was used very successfully in France until the mid-1980s [28] or scientists will create a new, zinc-based adjuvant as we already proposed [19,27]. ...
... We sincerely hope that scientists and doctors especially pediatricians, after taking notice of our work [19,27] and including this one, will implement our proposal for the removal of aluminum from vaccines and its replacement with Calcium Phosphate as the adjuvant which was used very successfully in France until the mid-1980s [28] or scientists will create a new, zinc-based adjuvant as we already proposed [19,27]. ...
... It is hoped that in the near future the scientists will create and introduce the safest and the most efficient aluminum free vaccine adjuvant. Until then once again, we suggest, we recommend an immediate postponement of vaccination of children with vaccines that use aluminum as an adjuvant, up to the age of 12 months [19,27]. ...
Aluminum is inevitable component of many vaccines. The benefit of the vaccines is undeniable but effects of aluminum toxicity might be underestimated and neglected. In this review, we highlighted the mechanims of aluminum toxicity, which is still in debate. So far, all the papers that disscused the adverse aluminum effects pointed two mechanisms responsible for Al toxicity, direct Al toxicity and aluminum induced cell damage via the oxidative metabolism. According to our knowledge, which is based on basic principles of biochemistry and inorganic chemisty, we suggested that aluminum highly interferes with iron metabolism eventually resulting in iron-mediated cell damage. More importantly, in this paper, we offered easily feasible solutions, in order to avoid alumium toxicity in the future. We suggest that as it once was, Calcium Phosphate again to be used as the adjuvant or even better solution that the vaccine adjuvant should be based on zinc compounds. Until an adequate adjuvant is provided, we suggest instant postponement of vaccination with vaccines which use aluminum as the adjuvant until the 12 months of age.
... Should the proposed suggestion for AdAl reduction according to the birth weights [4] be accepted, it seems that loading the infants with decreased vaccine antigens and decreased AdAl would almost certainly lead to decreased immune responses. Instead of decreasing AdAl, the following alternative solutions have already been proposed [6]: ...
... Until the early-1970s it was also successfully used in pentavalent human vaccinations (smallpox, yellow fever, measles, BCG, and tetanus), also without any reported adverse reactions [7]. Furthermore, it has already been suggested that zinc could be the element of choice to replace aluminium in vaccines [6]. ...
... Mercury present in food and in human milk in the form of methyl mercury as a divalent metal (Hg 2+ ) is adsorbed by an enterocytic divalent metal transporter (DMT1) [12]. As was previously reported [6], the only "physiological" access to Al into the bodies of newborns, infants and children is through vaccines in the form of AdAl. Alternatively, current immunization schedules with vaccines containing AdAl are given to infants, but thimerosal (as a vaccine preservative) is found mostly in vaccines used in non-industrialized countries [13]. ...
... Should the proposed suggestion for AdAl reduction according to the birth weights [4] be accepted, it seems that loading the infants with decreased vaccine antigens and decreased AdAl would almost certainly lead to decreased immune responses. Instead of decreasing AdAl, the following alternative solutions have already been proposed [6]: ...
... Until the early-1970s it was also successfully used in pentavalent human vaccinations (smallpox, yellow fever, measles, BCG, and tetanus), also without any reported adverse reactions [7]. Furthermore, it has already been suggested that zinc could be the element of choice to replace aluminium in vaccines [6]. ...
... Mercury present in food and in human milk in the form of methyl mercury as a divalent metal (Hg 2+ ) is adsorbed by an enterocytic divalent metal transporter (DMT1) [12]. As was previously reported [6], the only "physiological" access to Al into the bodies of newborns, infants and children is through vaccines in the form of AdAl. Alternatively, current immunization schedules with vaccines containing AdAl are given to infants, but thimerosal (as a vaccine preservative) is found mostly in vaccines used in non-industrialized countries [13]. ...
... ASD can present as a collection of health issues and comorbidities [8,9] not limited to neurodevelopmental, language, or social challenges, nor necessarily tied to genetic factors [10][11][12][13][14][15]. Comorbidities include immune dysregulation, [16][17][18][19][20][21][22][23] gastrointestinal issues such as diarrhea, constipation, and dysbiosis, mitochondrial dysfunction [24][25][26][27], poor detoxification [28], inflammation [29], food sensitivities, evidence of environmental toxicants [30][31][32][33][34][35][36][37][38][39][40][41][42], retained reflexes [43,44] and other structural or functional challenges. ...
The prevalence of autism has been increasing at an alarming rate. Even accounting for the expansion of autism spectrum disorder diagnostic (ASD) criteria throughout the 1990’s, there has been an over 300% increase in ASD prevalence since the year 2000. The often debilitating personal, familial, and societal sequelae of autism are generally believed to be lifelong. However, there have been several encouraging case reports demonstrating reversal of autism diagnoses with a therapeutic focus on addressing the environmental and modifiable lifestyle factors believed to be largely underlying the condition. This case report describes the reversal of autism among dizygotic, female twin toddlers and provides a review of related literature describing associations between modifiable lifestyle factors, environmental exposures, and various clinical approaches to treating autism. The twins were diagnosed with Level 3 severity ASD “requiring very substantial support” at approximately 20 months of age following concerns of limited verbal and non-verbal communication, repetitive behaviors, rigidity around transitions, and extensive gastrointestinal symptoms, among other common symptoms. A parent-driven, multidisciplinary, therapeutic intervention involving a variety of licensed clinicians focusing primarily on addressing environmental and modifiable lifestyle factors was personalized to each of the twin’s symptoms, labs, and other outcome measures. Dramatic improvements were noted within several months in most domains of the twins’ symptoms, which was manifested in reductions of Autism Treatment Evaluation Checklist (ATEC) scores from 76 to 32 in one of the twins and from 43 to 4 in the other twin. The improvement in symptoms and ATEC scores has remained relatively stable for six months at last assessment. While prospective studies are required, this case offers further encouraging evidence of ASD reversal through a personalized, multidisciplinary approach focusing predominantly on addressing environmental and lifestyle risk factors.
... Moreover, once again and now for the fourth time we call for the immediate suspension of all vaccination with vaccines that contain aluminum as an adjuvant for children aged up to 12 months, that is until the child starts walking and until scientists replace aluminum with calcium (as was the practice in France before 1985) or with zinc or a nonmetallic adjuvant such as microcrystalline tyrosine or monosodium urate. 14,15,23 At the same time, sustained efforts should be made to create so-called mucosal vaccines against diphtheria, pertussis, 24 measles, mumps and rubella. Meanwhile, all the children born to hepatitis B positive mothers, regardless of their place of birth (i.e., low risk or high-risk countries) must be vaccinated against hepatitis B, even with the current vaccines, as the benefits from vaccines by far outweigh potential harm caused by adjuvant aluminum. ...
Our aim is an achievement of a 100 percent vaccination rate without toxic vaccine effects. We did a comprehensive literature review on aluminum neurotoxicity and early neonatal hepatitis B vaccination. We analyzed indications for introduction of early neonatal hepatitis B vaccination and the data on experimental and clinical aluminum‐induced neurotoxicity. It is justified very early hepatitis B vaccination to be carried out in high‐risk endemic areas. In those countries there is a large number of hepatitis B positive individuals, including pregnant women, which leads to a great number of vertical, mother‐to‐child, transmissions of the virus during pregnancy. There is also a serious risk of perinatal Hepatitis B virus infections in such countries. Early neonatal hepatitis B vaccination is also carried out in low‐risk countries, where the number of hepatitis B positive pregnant women is extremely small, making the number of newborns who require the prevention of hepatitis B infection extremely small as well. It is necessary for all vaccines which contain aluminum as an adjuvant to be immediately suspended as children vaccination until they start walking and until aluminum is replaced with calcium, zinc or a nonmetallic adjuvant such as microcrystalline tyrosine or monosodium urate. Meanwhile sustained efforts should be made to create the so‐called mucosal vaccines against diphtheria, pertussis, measles, mumps and rubella. At the same time, all the children born to hepatitis B positive mothers, regardless of their place of birth must be vaccinated against hepatitis B as the benefits from vaccines by far outweigh potential harm caused by adjuvant aluminum.
... Almost 5 mg of aluminum from parenteral vaccines can surge into the infant's body (Miller, 2016). Regarding the fact that aluminum neurotoxicity was confirmed in mice experiments (Crepeaux et al., 2017) and clinical studies (Bishop et al., 1997), in 2019 it was proposed that non-toxic zinc compounds (hydroxide, sulfate, or phosphate) could be used as an adjuvant replacement, instead (Ivanovski et al., 2019). The presence of Al was detected at elevated levels in the brain tissue of patients with ASD (Mold et al., 2018). ...
The identification of biomarkers as diagnostic tools and predictors of response to treatment of neurological developmental disorders (NDD) such as schizophrenia (SZ), attention deficit hyperactivity disorder (ADHD), or autism spectrum disorder (ASD), still remains an important challenge for clinical medicine. Metallomic profiles of ASD patients cover, besides essential elements such as cobalt, chromium, copper, iron, manganese, molyb-denum, zinc, selenium, also toxic metals burden of: aluminum, arsenic, mercury, lead, beryllium, nickel, cad-mium. Performed studies indicate that children with ASD present a reduced ability of eliminating toxic metals, which leads to these metals' accumulation and aggravation of autistic symptoms. Extensive metallomic studies allow a better understanding of the importance of trace elements as environmental factors in the pathogenesis of ASD. Even though a mineral imbalance is a fact in ASD, we are still expecting relevant tests and the elaboration of reference levels of trace elements as potential biomarkers useful in diagnosis, prevention, and treatment of ASD.
... [65][66][67][68][69][70][71] Aluminium (Al) <10 µg/L (serum) Patients who are exposed to high doses of Al are presented with Al accumulation in both blood plasma and brain. The entering of Al to the CNS is [72][73][74][75][76][77][78][79] possible via transferrin and it mainly accumulates in those regions that are rich in transferrin receptors. Levels of Al, which might result in early symptoms of neurotoxicity are> 13 µg/L (plasma). ...
The alterations in serum trace element levels are common phenomena observed in patients with different psychiatric conditions such as schizophrenia, autism spectrum disorder, or major depressive disorder. The fluctuations in the trace element concentrations might act as potential diagnostic and prognostic biomarkers of many psychiatric and neurological disorders. This paper aimed to assess the alterations in serum trace element concentrations in patients with a diagnosed schizophrenia. The authors made a systematic review, extracting papers from the PubMed, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Among 5009 articles identified through database searching, 59 of them were assessed for eligibility. Ultimately, 33 articles were included in the qualitative synthesis. This review includes the analysis of serum levels of the following trace elements: iron, nickel, molybdenum, phosphorus, lead, chromium, antimony, uranium, magnesium, aluminum, zinc, copper, selenium, calcium, and manganese. Currently, there is no consistency regarding serum trace element levels in schizophrenic patients. Thus, it cannot be considered as a reliable prognostic or diagnostic marker of schizophrenia. However, it can be assumed that altered concentrations of those elements are crucial regarding the onset and exaggeration of either psychotic or negative symptoms or cognitive dysfunctions.
The prevalence of autism has been increasing at an alarming rate. Even accounting for the expansion of autism spectrum disorder diagnostic (ASD) criteria throughout the 1990’s, there has been an over 300% increase in ASD prevalence since the year 2000. The often debilitating personal, familial, and societal sequelae of autism are generally believed to be lifelong. However, there have been several encouraging case reports demonstrating the reversal of autism diagnoses, with a therapeutic focus on addressing the environmental and modifiable lifestyle factors believed to be largely underlying the condition. This case report describes the reversal of autism symptoms among dizygotic, female twin toddlers and provides a review of related literature describing associations between modifiable lifestyle factors, environmental exposures, and various clinical approaches to treating autism. The twins were diagnosed with Level 3 severity ASD “requiring very substantial support” at approximately 20 months of age following concerns of limited verbal and non-verbal communication, repetitive behaviors, rigidity around transitions, and extensive gastrointestinal symptoms, among other common symptoms. A parent-driven, multidisciplinary, therapeutic intervention involving a variety of licensed clinicians focusing primarily on addressing environmental and modifiable lifestyle factors was personalized to each of the twin’s symptoms, labs, and other outcome measures. Dramatic improvements were noted within several months in most domains of the twins’ symptoms, which manifested in reductions of Autism Treatment Evaluation Checklist (ATEC) scores from 76 to 32 in one of the twins and from 43 to 4 in the other twin. The improvement in symptoms and ATEC scores has remained relatively stable for six months at last assessment. While prospective studies are required, this case offers further encouraging evidence of ASD reversal through a personalized, multidisciplinary approach focusing predominantly on addressing modifiable environmental and lifestyle risk factors.
The multifactorial etiology of major depressive disorder (MDD) includes biological, environmental, genetic, and psychological aspects. Recently, there has been an increasing interest in metallomic studies in psychiatry, aiming to evaluate the role of chosen trace elements in the MDD etiology as well as the progression of symptoms. This narrative review aims to summarize the available literature on the relationship between the concentration of chosen elements in the serum of patients with MDD and the onset and progression of this psychiatric condition. The authors reviewed PubMed, Web of Science, and Scopus databases searching for elements that had been investigated so far and further evaluated them in this paper. Ultimately, 15 elements were evaluated, namely, zinc, magnesium, selenium, iron, copper, aluminium, cadmium, lead, mercury, arsenic, calcium, manganese, chromium, nickel, and phosphorus. The association between metallomic studies and psychiatry has been developing dynamically recently. According to the results of current research, metallomics might act as a potential screening tool for patients with MDD while at the same time providing an assessment of the severity of symptoms. Either deficiencies or excessive amounts of chosen elements might be associated with the progression of depressive symptoms or even the onset of the disease among people predisposed to MDD.
A dual-function probe BHMH was synthesized and characterized functioned with benzothiazole as signal unit for the simultaneous detection of Zn²⁺ and Al³⁺ DMF/H2O (1/1, v/v, 0.01 M HEPES, pH = 6.0). Probe BHMH achieved in the recognition of Zn²⁺ and Al³⁺ both through obvious fluorescence turn-on and absorbance ratiometric response. The limit of detection (LOD) according to the titration of fluorescence for Zn²⁺ and Al³⁺ were 1.27 × 10⁻⁷ M and 1.42 × 10⁻⁷ M, respectively. Furthermore, the significant color changes could be detected by naked eye whatever under ultraviolet-lamp or daylight. According to Job plot, the binding ratio of BHMH with Zn²⁺ and Al³⁺ were determined as 1:1 and 2:1, respectively. The binging detail was further confirmed by ¹H NMR titration and ESI-MS analysis as well. Moreover, probe BHMH was successfully applied in the detection Zn²⁺ and Al³⁺ in real sample and test stripe.
FDA regulations require safety testing of constituent ingredients in drugs (21 CFR 610.15). With the exception of extraneous proteins, no component safety testing is required for vaccines or vaccine schedules. The dosing of aluminum in vaccines is based on the production of antibody titers, not safety science. Here we estimate a Pediatric Dose Limit that considers body weight. We identify several serious historical missteps in past analyses of provisional safe levels of aluminum in vaccines, and provide updates relevant to infant aluminum exposure in the pediatric schedule considering pediatric body weight. When aluminum doses are estimated from Federal Regulatory Code given body weight, exposure from the current vaccine schedule are found to exceed our estimate of a weight-corrected Pediatric Dose Limit. Our calculations show that the levels of aluminum suggested by the currently used limits place infants at risk of acute, repeated, and possibly chronic exposures of toxic levels of aluminum in modern vaccine schedules. Individual adult exposures are on par with Provisional Tolerable Weekly Intake “limits”, but some individuals may be aluminum intolerant due to genetics or previous exposures. Vaccination in neonates and low birth-weight infants must be re-assessed; other implications for the use of aluminum-containing vaccines, and additional limitations in our understanding of neurotoxicity and safety levelsof aluminum in biologics are discussed.
Project page: http://ipaknowledge.org/Pediatric-Dosing-of-Aluminum.php
Aluminum is a neurotoxin, yet infants and young children are repeatedly injected with aluminum adjuvants from multiple vaccines during critical periods of brain development. Numerous studies provide credible evidence that aluminum adversely affects important biological functions and may contribute to neurodegenerative and autoimmune disorders. It is impossible to predetermine which vaccinated babies will succumb to aluminum poisoning. Aluminum-free health options are needed.
Introduction: Calcium phosphate was used as an adjuvant in France in diphtheria, tetanus, pertussis and poliomyelitis vaccines. It was later completely substituted by alum salts in the late 80’s, but it still remains as an approved adjuvant for the World Health Organization for human vaccination.
Area covered: Thus, calcium phosphate is now considered as one of the substances that could replace alum salts in vaccines. The aim of this paper is to draw a review of existing data on calcium phosphate as an adjuvant in order to bring out the strengths and weaknesses for its use on a large scale.
Expert commentary: Calcium phosphate is a compound naturally present in the organism, safe and already used in human vaccination. Beyond comparisons with the other adjuvants, calcium phosphate represents a good candidate to replace or to complete alum salts as a vaccine adjuvant.
Long-term biodistribution of nanomaterials used in medicine is largely unknown. This is the case for alum, the most widely used vaccine adjuvant, which is a nanocrystalline compound spontaneously forming micron/submicron-sized agglomerates. Although generally well tolerated, alum is occasionally detected within monocyte-lineage cells long after immunization in presumably susceptible individuals with systemic/neurologic manifestations or autoimmune (inflammatory) syndrome induced by adjuvants (ASIA).
On the grounds of preliminary investigations in 252 patients with alum-associated ASIA showing both a selective increase of circulating CCL2, the major monocyte chemoattractant, and a variation in the CCL2 gene, we designed mouse experiments to assess biodistribution of vaccine-derived aluminum and of alum-particle fluorescent surrogates injected in muscle. Aluminum was detected in tissues by Morin stain and particle induced X-ray emission) (PIXE) Both 500 nm fluorescent latex beads and vaccine alum agglomerates-sized nanohybrids (Al-Rho) were used.
Intramuscular injection of alum-containing vaccine was associated with the appearance of aluminum deposits in distant organs, such as spleen and brain where they were still detected one year after injection. Both fluorescent materials injected into muscle translocated to draining lymph nodes (DLNs) and thereafter were detected associated with phagocytes in blood and spleen. Particles linearly accumulated in the brain up to the six-month endpoint; they were first found in perivascular CD11b+ cells and then in microglia and other neural cells. DLN ablation dramatically reduced the biodistribution. Cerebral translocation was not observed after direct intravenous injection, but significantly increased in mice with chronically altered blood-brain-barrier. Loss/gain-of-function experiments consistently implicated CCL2 in systemic diffusion of Al-Rho particles captured by monocyte-lineage cells and in their subsequent neurodelivery. Stereotactic particle injection pointed out brain retention as a factor of progressive particle accumulation.
Nanomaterials can be transported by monocyte-lineage cells to DLNs, blood and spleen, and, similarly to HIV, may use CCL2-dependent mechanisms to penetrate the brain. This occurs at a very low rate in normal conditions explaining good overall tolerance of alum despite its strong neurotoxic potential. However, continuously escalating doses of this poorly biodegradable adjuvant in the population may become insidiously unsafe, especially in the case of overimmunization or immature/altered blood brain barrier or high constitutive CCL-2 production.
This MiniReview updates and expands the MiniReview of aluminium toxicokinetics by Wilhelm et al. published by this journal in 1990. The use of 26Al, analyzed by accelerator mass spectrometry, now enables determination of Al toxicokinetics under physiological conditions. There is concern about aluminium in drinking water. The common sources of aluminium for man are reviewed. Oral Al bioavailability from water appears to be about 0.3%. Food is the primary common source. Al bioavailability from food has not been adequately determined. Industrial and medicinal exposure, and perhaps antiperspirant use, can significantly increase absorbed aluminium. Inhalation bioavailability of airborne soluble Al appears to be about 1.5% in the industrial environment. Al may distribute to the brain from the nasal cavity, but the significance of this exposure route is unknown. Systemic Al bioavailability after single underarm antiperspirant application may be up to 0.012%. All intramuscularly injected Al, e.g. from vaccines, may eventually be absorbed. Al distributes unequally to all tissues. Distribution and renal excretion appear to be enhanced by citrate. Brain uptake of Al may be mediated by Al transferrin and Al citrate complexes. There appears to be carrier-mediated efflux of Al citrate from the brain. Elimination half-lives of years have been reported in man, probably reflecting release from bone. Al elimination is primarily renal with ≤2% excreted in bile. The contribution of food to absorbed Al needs to be determined to advance our understanding of the major components of Al toxicokinetics.
The brain is a highly compartmentalized organ exceptionally susceptible to accumulation of metabolic errors. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of the elderly and is characterized by regional specificity of neural aberrations associated with higher cognitive functions. Aluminum (Al) is the most abundant neurotoxic metal on earth, widely bioavailable to humans and repeatedly shown to accumulate in AD-susceptible neuronal foci. In spite of this, the role of Al in AD has been heavily disputed based on the following claims: 1) bioavailable Al cannot enter the brain in sufficient amounts to cause damage, 2) excess Al is efficiently excreted from the body, and 3) Al accumulation in neurons is a consequence rather than a cause of neuronal loss. Research, however, reveals that: 1) very small amounts of Al are needed to produce neurotoxicity and this criterion is satisfied through dietary Al intake, 2) Al sequesters different transport mechanisms to actively traverse brain barriers, 3) incremental acquisition of small amounts of Al over a lifetime favors its selective accumulation in brain tissues, and 4) since 1911, experimental evidence has repeatedly demonstrated that chronic Al intoxication reproduces neuropathological hallmarks of AD. Misconceptions about Al bioavailability may have misled scientists regarding the significance of Al in the pathogenesis of AD. The hypothesis that Al significantly contributes to AD is built upon very solid experimental evidence and should not be dismissed. Immediate steps should be taken to lessen human exposure to Al, which may be the single most aggravating and avoidable factor related to AD.
Aluminum, a contaminant of commercial intravenous-feeding solutions, is potentially neurotoxic. We investigated the effect of perinatal exposure to intravenous aluminum on the neurologic development of infants born prematurely.
We randomly assigned 227 premature infants with gestational ages of less than 34 weeks and birth weights of less than 1850 g who required intravenous feeding before they could begin enteral feeding to receive either standard or specially constituted, aluminum-depleted intravenous-feeding solutions. The neurologic development of the 182 surviving infants who could be tested was assessed by using the Bayley Scales of Infant Development at 18 months of age.
The 90 infants who received the standard feeding solutions had a mean (+/-SD) Bayley Mental Development Index of 95+/-22, as compared with 98+/-20 for the 92 infants who received the aluminum-depleted solutions (P=0.39). In a planned subgroup analysis of infants in whom the duration of intravenous feeding exceeded the median and who did not have neuromotor impairment, the mean values for the Bayley Mental Development Index for the 39 infants who received the standard solutions and the 41 infants who received the aluminum-depleted solutions were 92+/-20 and 102+/-17, respectively (P=0.02). The former were significantly more likely (39 percent, vs. 17 percent of the latter group; P=0.03) to have a Mental Development Index of less than 85, increasing their risk of subsequent educational problems. For all 157 infants without neuromotor impairment, increasing aluminum exposure was associated with a reduction in the Mental Development Index (P=0.03), with an adjusted loss of one point per day of intravenous feeding for infants receiving the standard solutions.
In preterm infants, prolonged intravenous feeding with solutions containing aluminum is associated with impaired neurologic development.
Oral aluminum (Al) bioavailability from drinking water has been previously estimated, but there is little information on Al bioavailability from foods. It was suggested that oral Al bioavailability from drinking water is much greater than from foods. The objective was to further test this hypothesis. Oral Al bioavailability was determined in the rat from basic [26Al]-sodium aluminum phosphate (basic SALP) in a process cheese. Consumption of approximately 1g cheese containing 1.5% or 3% basic SALP resulted in oral Al bioavailability (F) of approximately 0.1% and 0.3%, respectively, and time to maximum serum 26Al concentration (Tmax) of 8-9h. These Al bioavailability results were intermediate to previously reported results from drinking water (F approximately 0.3%) and acidic-SALP incorporated into a biscuit (F approximately 0.1%), using the same methods. Considering the similar oral bioavailability of Al from food vs. water, and their contribution to the typical human's daily Al intake ( approximately 95% and 1.5%, respectively), these results suggest food contributes much more Al to systemic circulation, and potential Al body burden, than does drinking water. These results do not support the hypothesis that drinking water provides a disproportionate contribution to total Al absorbed from the gastrointestinal tract.
Autism spectrum disorder is a neurodevelopmental disorder of unknown aetiology. It is suggested to involve both genetic susceptibility and environmental factors including in the latter environmental toxins. Human exposure to the environmental toxin aluminium has been linked, if tentatively, to autism spectrum disorder. Herein we have used transversely heated graphite furnace atomic absorption spectrometry to measure, for the first time, the aluminium content of brain tissue from donors with a diagnosis of autism. We have also used an aluminium-selective fluor to identify aluminium in brain tissue using fluorescence microscopy. The aluminium content of brain tissue in autism was consistently high. The mean (standard deviation) aluminium content across all 5 individuals for each lobe were 3.82(5.42), 2.30(2.00), 2.79(4.05) and 3.82(5.17) μg/g dry wt. for the occipital, frontal, temporal and parietal lobes respectively. These are some of the highest values for aluminium in human brain tissue yet recorded and one has to question why, for example, the aluminium content of the occipital lobe of a 15 year old boy would be 8.74 (11.59) μg/g dry wt.? Aluminium-selective fluorescence microscopy was used to identify aluminium in brain tissue in 10 donors. While aluminium was imaged associated with neurones it appeared to be present intracellularly in microglia-like cells and other inflammatory non-neuronal cells in the meninges, vasculature, grey and white matter. The pre-eminence of intracellular aluminium associated with non-neuronal cells was a standout observation in autism brain tissue and may offer clues as to both the origin of the brain aluminium as well as a putative role in autism spectrum disorder.
Aluminium (Al) oxyhydroxide (Alhydrogel®), the main adjuvant licensed for human and animal vaccines, consists of primary nanoparticles that spontaneously agglomerate. Concerns about its safety emerged following recognition of its unexpectedly long-lasting biopersistence within immune cells in some individuals, and reports of chronic fatigue syndrome, cognitive dysfunction, myalgia, dysautonomia and autoimmune/inflammatory features temporally linked to multiple Al-containing vaccine administrations. Mouse experiments have documented its capture and slow transportation by monocyte-lineage cells from the injected muscle to lymphoid organs and eventually the brain. The present study aimed at evaluating mouse brain function and Al concentration 180 days after injection of various doses of Alhydrogel® (200, 400 and 800 μg Al/kg of body weight) in the tibialis anterior muscle in adult female CD1 mice. Cognitive and motor performances were assessed by 8 validated tests, microglial activation by Iba-1 immunohistochemistry, and Al level by graphite furnace atomic absorption spectroscopy.
Objectives:
To compare motor, cognitive and language characteristics in children aged 18 months who were prenatally exposed to low-level methyl-mercury (MeHg), and to analyze the eventual differences in these characteristics in relation to cord blood THg concentration.
Patients and methods:
The total number of 205 child-mother pairs was included in the study, and total cord blood mercury was measured in 198 of them. Out of the 198 already measured samples, 47 of them have also been tested for methyl-mercury in cord blood. Data regarding the 47 samples of MeHg levels has been used for calculating the correlation between cord blood THg and cord blood MeHg. MeHg and THg showed a significant correlation (r=0.95, p<0.05). One month after the delivery, mothers were asked to complete the questionnaire regarding socioeconomic factors, breastfeeding of their infants, and dietary habits during pregnancy. Neurodevelopmental assessment of motor, cognitive and language skills were conducted on 168 children using The Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Regarding the cord blood THg concentration, 135 children were divided in 4 quartile groups. Their neurodevelopmental characteristics have been compared.
Results:
The cord blood THg concentration median and inter-quartile range was 2.98ng/g (1.41-5.61ng/g). There was a negative correlation between cord blood THg concentration and fine motor skills (rho=-0.22, p=0.01). It is evident that children grouped in 2nd ,3rd and 4th quartile had statistically significant lower fine motor skills assessment related to those grouped in 1st quartile (2nd quartile -1.24, p=0.03; 3rd quartile -1.28, p=0.03; 4th quartile -1.45, p=0.01). The differences in fine motor skills assessments between children in 2nd and 3rd and 3rd and 4th quartile were not statistically significant.
Conclusion:
Intrauterine exposure to low-level THg (MeHg) is associated with alterations in fine motor skills at the age of 18 months.
I. INTRODUCTION
During a period of about seven years I have occasionally conducted experiments on the effects of aluminum salts. These studies have convinced me that the use in food of alum or any other aluminum compound is a dangerous practice. That the aluminum ion is very toxic is well known. That"aluminized" food yields soluble aluminum compounds to gastric juice (and stomach contents) has been demonstrated. That such soluble aluminum is in part absorbed and carried to all parts of the body by the blood can no longer be doubted. That the organism can "tolerate" such treatment without suffering harmful consequences has not been shown. It is believed that the facts in this paper will give emphasis to my conviction that aluminum should be excluded from food.1II. EXPERIMENTS BY HOUSE AND GIES ON THE EFFECTS OF ALUMINUM COMPOUNDS ON THE GROWTH OF SEEDLINGS
Several years ago, in collaboration
In vitro dissolution experiments although perhaps not at typical body concentrations and temperatures demonstrated that the alpha-hydroxycarboxylic acids present in interstitial fluid (citric acid, lactic acid, and malic acid) are capable of dissolving aluminum-containing adjuvants. Amorphous aluminum phosphate adjuvant dissolved more rapidly than crystalline aluminum hydroxide adjuvant. Intramuscular administration in New Zealand White rabbits of aluminum phosphate and aluminum hydroxide adjuvants, which were labelled with 26Al, revealed that 26Al was present in the first blood sample (1 h) for both adjuvants. The area under the blood level curve for 28 days indicated that three times more aluminum was absorbed from aluminum phosphate adjuvant than aluminum hydroxide adjuvant. In vivo studies using 26Al-labelled adjuvants are relatively safe because accelerator mass spectrometry (AMS) can quantify quantities of 26Al as small as 10(-17) g. A similar study in humans would require a whole-body exposure of 0.7 microSv per year compared to the natural background exposure of 3000 microSv per year. The in vitro dissolution and in vivo absorption studies indicate that aluminum-containing adjuvants which are administered intramuscularly are dissolved by alpha-hydroxycarboxylic acids in interstitial fluid, absorbed into the blood, distributed to tissues, and eliminated in the urine.
1. Aluminum is neurotoxic in humans and animals and alters formation of inositol phosphate (IP) second messengers following in vivo or in vitro exposure. 2. Several components of the IP signalling system including G-proteins, phosphatidylinositol-specific phospholipase C (PI-PLC), protein kinase C (PKC) and Ca2+ homeostasis are susceptible to inhibition/disruption by aluminum compounds. 3. Recent evidence suggests that, despite its effects on other components, competitive inhibition by aluminum of phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis by PI-PLC underlies its effects on agonist-stimulated IP generation.
Calcium is actively transported into intracellular organelles and out of the cytoplasm by Ca2+/Mg(2+)-ATPases located in the endoplasmic reticulum and plasma membranes. We studied the effects of aluminum on calcium transport in the adult rat brain. We examined 45Ca-uptake in microsomes and Ca(2+)-ATPase activity in microsomes and synaptosomes isolated from the frontal cortex and cerebellum of adult male Long-Evans rats. ATP-dependent 45Ca-uptake was similar in microsomes from both brain regions. The addition of 50-800 microM AlCl3 resulted in a concentration-dependent inhibition of 45Ca-uptake. Mg(2+)-dependent Ca(2+)-ATPase activity was significantly lower in synaptosomes compared to microsomes in both frontal cortex and cerebellum. In contrast to the uptake studies, AlCl3 stimulated Mg(2+)-dependent Ca(2+)-ATPase activity in both microsomes and synaptosomes from both brain regions. To determine the relationship between aluminum and Mg2+, we measured ATPase activity in the presence of increasing concentrations of Mg2+ or AlCl3. Maximal ATPase activity was obtained between 3 and 6 mM Mg2+. When we substituted AlCl3 for Mg2+, ATPase activity was also stimulated in a concentration-dependent manner, but to a greater extent than with Mg2+. One interpretation of these data is that aluminum acts at multiple sites to displace both Mg2+ and Ca2+, increasing the activity of the Ca(2+)-ATPase, but disrupting transport of calcium.
Safety of aluminum from dietary intake, scientific opinion of the panel on food additives, flavourings, processing aids and food contact materials, AFC)
EFSA (European Food Safety Authority), Safety of aluminum from dietary intake,
scientific opinion of the panel on food additives, flavourings, processing aids and
food contact materials, AFC). EFSA J. (2008) 1-34.